Extracorporeal circulation during cardiac surgery is characterized with increased risk for hypercoagulation because blood is exposed to foreign, nonendothelial cell surfaces. Thus, the usage of extracorporeal circulation is essentially not possible without anticoagulation. Open-heart surgery as well as many perioperative factors, such as acidosis, hypocalcemia, hypothermia, and hemodilution, might affect hemostasis and lead to coagulopathy and bleeding. A new insight into the effectiveness of anticoagulant therapy is applied to modify the dosing regimen with respect to the genetic CYP2C9 and VKORC1allelic variants. A systematic literature search was performed for VKORC1 and CYP2C9 and their association with coumarin anticoagulant therapy and bleeding risk in postoperative period of cardiac surgery with extracorporeal circulation.